How do they ensure that antibodies for the spike protein don't interfere with other processes in the body? E.g. if the spike protein bears a sufficient resemblance to part of another protein expressed by healthy human tissue, is there a risk of an immune response? Presumably the Phase 1 trial would sort that out for the most part, just wondering if there is any kind of ability to screen for that ahead of time.
The viral spike proteins aren’t like other proteins the float around in your body, but the are like the proteins on other viruses. Your immune system also has a baroque system for determining which things in your body belong to you.
Do we really know this? Obviously the spike proteins are using an existing mechanism (ACE2) in our bodies to bind to cells. Of primary importance to both viruses and our reproductive system is the membrane fusion function for instance. We must also consider how our bodies developed in the first place; “RNA world” and “virus world” theories predict our genetics evolved from RNA-based processes or even a primordial graveyard of viral RNA.
We also don’t fully understand what causes autoimmune disease, but various environmental causes have been explored including bacterial and viral infections. Presumably if a viral infection could trigger an autoimmune response in certain genetically predisposed groups, then so could a vaccine designed to mimic a virus.
Unfortunately the incentives in our medical system are not designed to find cures for autoimmune diseases, although they are very much incentivized for palliative care, so progress has been painfully slow in understanding the deeper complexities of the immune system.
> Presumably if a viral infection could trigger an autoimmune response in certain genetically predisposed groups, then so could a vaccine designed to mimic a virus.
This is true. Some of the extremely rare auto-immune issues that have impacted people who have been vaccinated for specific flu viruses in, IIRC, 1976 and 2009, were thought to occur at even higher rates and severity with people who contracted the virus. So, vaccination might impact you, but likely worse the the virus itself due to the greater amount of virus in your system.
I am not a scientist, but I would expect that the mRNA vaccines would have less of a chance of having an auto-immune reaction since they contain only one of the many proteins contained in the actual virus.
Yeah, I’m actually very hopeful that mRNA medicine will be able to overcome issues like these in ways traditional vaccines couldn’t. For example, variations could be developed that are more effective for each racial group, rather than a one-size-fits all approach that may be biased. From there, perhaps even individuals who have autoimmune disease markers could have variants developed for them as well.
There are definitely phenotypical variations in humans that have health implications. To the extent that some of these are adaptive to region they may align with the rather poorly defined buckets we call ‘race’.
To GP’s point, lack of diversity in clinical trials can result in medicines that vary in efficacy and safety in the broader population. The ability to customize a therapy to an individual would help reduce the impact of this issue.
AFAIK there are no human races from a taxonomic point of view, all human beings belong to the same subspecies. There are of course genetic differences between individuals and ethnic groups though, otherwise we would be all identical twins (the point is not condemning the differences - differences are in general a good thing - the point is not attaching value judgements to the differences).
Subspecies definitions can be rather arbitrary in general, and don't fit well to a species with the technology of humans.
1000 years ago you probably could have said that indigenous subsaharan Africans and Americans are different subspecies of homo sapiens simply because one group has darker brown skin and lives in Africa, and one has lighter brown skin and lives in the Americas (phenotype difference + range difference is all it takes). But today the "native range" of every ethnic group is essentially global due to airplanes and immigration, so you'd probably say we're all one subspecies. But either way, the label "subspecies" conveys far less information than people sometimes assign it.
Since 23andMe can figure out your geographic origin from your DNA there must be differences. Studying the nature of these differences might make some people uncomfortable but just as with subtle male/female differences, these studies could lead to amazing improvements in medical treatment.
>I am not a scientist, but I would expect that the mRNA vaccines would have less of a chance of having an auto-immune reaction since they contain only one of the many proteins contained in the actual virus.
This is the angle that, for me, is suppressing my innate concern for a widescale and rapid application of a brand new immunological therapy. It's extremely targeted and feels like the future. I can imagine a day where the FDA approves the process rather than the instance of mRNA-based therapies, allowing for highly personalized treatment.
> Do we really know this? Obviously the spike proteins are using an existing mechanism (ACE2) in our bodies to bind to cells.
Sure, but aren't the proteins produced by the vaccine virtually identical to the ones produced by the actual virus?
If so, the calculus looks like this:
1) Take the vaccine and accept the (unknown, but apparently quite small) probability that something in your body will react very negatively to the generated viral proteins.
2) Get the virus, accept the probability (also unknown, but the same as in 1) that something in your body will react very negatively to the viral proteins, plus accept the additional risk of being infected by the actual virus.
I guess the third possibility would be to refuse the vaccine and gamble that you won't get the virus, either.
It’s not clear if the vaccine will prevent infectiousness yet, unfortunately, so for now it’s best to assume even vaccinated people can spread the virus until more is known. Both ways will increase herd immunity.
I generally agree with you. Keep in mind I'm at 'stayed at the Holiday Inn' levels of competence here, but in my mind the spike proteins that are generated by an actual infection don't typically leave the cytoplasm detached from the rest of the virus. This could be incorrect.
If that's generally true, the difference here would be that the part of the spike protein topology that is typically bound to other proteins in an actual infection would be accessible to the immune system in the case of a vaccination. I think that is where the differential risk could occur with a vaccination that wouldn't occur with an actual infection (however small that might be).
In my daughter's case, something happened when she was about 14 years old that caused her body to determine that the beta cells in her pancreas were invaders and have to die, so I'm just tuned into this kind of possible side effect.
> (...) but in my mind the spike proteins that are generated by an actual infection don't typically leave the cytoplasm detached from the rest of the virus.
If the virus is destroyed and released into the extracellular environment, its proteins can dissociate and are further fragmented and processed by the immune system. What’s usually presented to T cells are small antigen pieces as opposed to the whole virus/protein.
> in my mind the spike proteins that are generated by an actual infection don't typically leave the cytoplasm detached from the rest of the virus
Virus takes over the cell, makes the cell to manufacture components of the virus and to assemble viruses, until this disrupts the cell so bad that the cell dies and typically bursts. Surely at this point, not only assembled viruses, but also components at different stages of production, are released?
Thank you. I knew this at some level but this (amazing) animation of HIV got me on a track of thinking that the viruses have a mechanism for exiting the cell without destroying it:
Like the Wikipedia article says, most viruses make the cell burst. Some, like HIV, have less destructive methods. I could not find how SARS-CoV-2 does it.
I read that the immune system doesn't usually produce antibodies for the spike protein when fighting the virus, i think it was a membrane protein that was more commonly targeted, and we didn't understand why.
Apparently, protein (Syncytin-1) present in the spike of SARS-COV2 is also present in human placenta. If the vaccine produces anti-bodies for this protein, it could also lead to infertility in women.
I think the answer to this questions would be nice to have.
"Several vaccine candidates are expected to induce the formation of humoral antibodies against spike proteins of SARS-CoV-2. Syncytin-1 (see Gallaher, B., “Response to nCoV2019 Against Backdrop of Endogenous Retroviruses” - http://virological.org/t/response-to-ncov2019- against-backdrop-of-endogenous-retroviruses/396), which is derived from human endogenous retroviruses (HERV) and is responsible for the development of a placenta in mammals and humans and is therefore an essential prerequisite for a successful pregnancy, is also found in homologous form in the spike proteins of SARS viruses. There is no indication whether antibodies against spike proteins of SARS viruses would also act like anti-Syncytin-1 antibodies. However, if this were to be the case this would then also prevent the formation of a placenta which would result in vaccinated women essentially becoming infertile. To my knowledge, Pfizer/BioNTech has yet to release any samples of written materials provided to patients, so it is unclear what, if any, information regarding (potential) fertility-specific risks caused by antibodies is included."
> Jacob Yount, an associate professor of the department of microbial infection and immunity at Ohio State University, College of Medicine, has studied the syncytin proteins as well as SARS-CoV-2. Yount said the COVID vaccines do not contain syncytin-1 protein or mRNA encoding syncytin-1, and thus there is no reason to think that an immune response against syncytin-1 would be developed.
> “We don’t see infertility with the flu vaccine and that is also targeting a viral fusion protein in a similar way that the spike is a viral fusion protein of the coronavirus,” he said.
We do know the vaccine DOES contain PART of the syncytin-1 sequence. Is it going to be a problem? We do not know.
This professor doesn't know about how much of the sequence is copied. He doesn't know the widespread affect of mRNA vaccines because we're in new territory here and it's possible that the risk of autoimmune responses is higher with such vaccines. He should know better than to equate mRNA vaccines with more traditional vaccines.
With every vaccine, a small percentage of people suffer adverse and autoimmune effects.
As that professor well knows, we're NOT discussing possibility (with that billions of people lined up, it's all but inevitable). Instead, we're discussing PROBABILITY that it will happen and how many people will be adversely affected.
I'm not saying the vaccine is bad or that people should freak out and not get vaccinated (even some vaccines with high complication rates have historically been much more helpful than harmful). I'm pointing out that while the intentions of the professor may be good, they're definitely not speaking the absolute truth and aren't actually in a position to know all the actual details about the vaccine.
I shared the link because I hadn't heard about the infertility risk before and I found a lot of conflicting information when I looked it up – with many main stream sources dismissing the claim out of hand.
My understanding is that, yes, the proteins are similar, but not the same, and that a similar protein also exists in influenza which does not cause infertility when targeted by our antibodies. I assume this doesn't mean that it couldn't cause infertility in the case of a COVID-19 vaccine, but it would suggest it's perhaps unlikely.
Is there any reason to believe an mRNA vaccine would be anymore likely to cause our antibodies to target the syncytin-1 spike protein as opposed to a more traditional vaccine?
I do agree with your point that it's more a question of the probability of side effects than a possibility. This is something that's bothered me about the attacks on those who are hesitant on the safety of these vaccines. Although I'm sure there's a very low risk that someone will suffer any adverse effects from these vaccines there is almost certainly going to be some cases of adverse side effects, so in the interest of public trust in the COVID-19 vaccines and all future vaccines we should be ensuring the public understand the risks fully and not attacking anyone for asking questions or expressing doubts, because if it does turn out that some of those doubts did indeed hold merit then no one will trust a word the media or professors have to say on this in the future.
Those developing the vaccine likely studied which viral epitopes (structural elements of the virus, consisting of multiple amino acids in a specific folded conformation) were recognized by antibodies from previously infected individuals. The frequency with which antibodies from different individuals are specific to any given epitope can indicate which epitopes might be best used in a vaccine.
> Tissue cross-reactivity assay is a standard method based on immunohistochemistry, required prior to phase I human studies for therapeutic antibodies.
EDIT: The mRNA vaccines are obviously not therapeutic antibodies, but they probably checked for cross-reactivity of the engineered spike protein as well as the generated antibodies using similar methods. I’m not 100% sure, though.
> EDIT: The mRNA vaccines are obviously not therapeutic antibodies, but they probably checked for cross-reactivity of the engineered spike protein as well as the generated antibodies using similar methods. I’m not 100% sure, though.
There is a study[0] showing cross-reactivity between SARS-CoV-2 antibodies and other human tissues, thus predisposing the host to autoimmune diseases. This should apply even more so to any vaccine since vaccines produce a more robust immune response.
Phase 2/3 of Pfizer-BioNTech did, however, include people with autoimmune diseases [1]. Other vaccine trials did not, as far as I am aware. This does not really shine a light on pre-disposition to an autoimmune disease 6-9-12 mo down the road.
Reading this comment again before I post made me realize it sounds very gloomy, so I feel obliged to say I'll be getting whatever vaccine I can get my hands on at the soonest possible date.
> There is a study[0] showing cross-reactivity between SARS-CoV-2 antibodies and other human tissues, thus predisposing the host to autoimmune diseases. This should apply even more so to any vaccine since vaccines produce a more robust immune response.
Since the antibody tested in the study was a commercial, monoclonal one, this is somewhat hard to assess. But I think you’re right given what they found in the blood tests.
> This does not really shine a light on pre-disposition to an autoimmune disease 6-9-12 mo down the road.
Autoimmune reactions should happen in the short run, right?
The important to thing to realize about Pandermix was that the rate of people impact was so small that even if we followed 50k phase 3 participants over 10 years, we wouldn't have uncovered the issue.
The narcolepsy issue was never going to be uncovered before it was rolled out large scale.
Not OP, but I feel similarly. I'm going to go get the vaccine as soon as I can because what's the alternative? I want to go to concerts and travel again. If I don't get the vaccine my choices are:
1) not care and probably get COVID-19, which has a chance of developing the same autoimmune issues that have been discussed
2) hide in my room for another unspecified length of time.
It is at this point that I remind myself of all the other dangerous things that I do: driving, motorcycling, rock climbing, skiing, etc.
The risk of long term side effects is worth the benefit of spinning up the global economy again.
ACE-2 is a popular target for blood-pressure related medications, but I highly doubt the vaccine is creating enough spike proteins to cause a systemic effect. Otherwise you'd see people showing up with oxygenation and other blood/lung related issues, just like actual COVID patients. You just create a little bit of spike protein to give your immune system a benign target to work off of.
One thing I haven't been able to find yet is how many spike proteins are generated per strand of mRNA. Is it 1:1 or is the mRNA reused a few/buncha times before it degrades?
I don't know, but I think that if it was just 1:1 it would be far easier to get the protein manufactured by cells living in a petri dish (that can be subjected to much more drastic changes) and inject those protein copies directly instead of mRNA wrapped in some fancy vector molecules.
The fancy vector molecules are just oils. AFAIK the reason they use mRNA is precisely because it's easy to make lots of it quickly through simple chemical processes. Proteins are much more complex, and harder to synthesize using traditional chemical processes.
Whoa. That's cool. A while back I wondered if we could just synthesize the proteins externally, but this way we only have to figure out how to synthesize, package and deliver mRNA and the process could be used to generate an arbitrary set of proteins. Presumably the proteins themselves are going to vary as much as the tissues in the human body, so the synthesis might be the same but the packaging and delivery parts would seem to vary widely based on characteristics of the protein.
To the best of my knowlede, the Novavax vaccine actually does this. Instead of delivering an mRNA nanoparticle, it delivers a spike protein nanoparticle. In fact, they just started phase 3 trials: https://www.sciencemag.org/news/2020/12/novavax-launches-piv...
It doesn't directly address your question, but it does show how the vaccine performs to control (labeled pbs) in terms of viral load and immune system activity when challenged with a dose of the virus.
My understanding is the mRNA is reused over and over-- the AAAAAAs at the end of the vaccine sequence are there to extend their tiny little lives a bit as the end breaks off after each reading.
It is reused many times as this super interesting article that I highly recommend [0] explains and I'll quote:
The very end of mRNA is polyadenylated. This is a fancy way of saying it ends on a lot of AAAAAAAAAAAAAAAAAAA. Even mRNA has had enough of 2020 it appears.
mRNA can be reused many times, but as this happens, it also loses some of the A’s at the end. Once the A’s run out, the mRNA is no longer functional and gets discarded. In this way, the ‘poly-A’ tail is protection from degradation.
Studies have been done to find out what the optimal number of A’s at the end is for mRNA vaccines. I read in the open literature that this peaked at 120 or so.
I love the image of the mRNA yelling AAAAAAAAAAA throughout the body warning of the virus that is about to come (and then slowly losing energy and dissolving into nothing as all screams do).
It tends to 'degrade' from the end, which is why all of the additional 'A' nucleotides are tacked on to the end, it's basically a NOOP sled that gets shorter and shorter until the instance is disabled.
The mRNA isn't intended to be copied in the body. Once the dose is used up there should be no more spike proteins created.
As someone who takes an ACE inhibitor, I've just tried to read up and ACE inhibitors are for ACE-1, not ACE-2. They are two different things. ACE-1 is a precursor that generates the protein/enzyme that eventually connects to the ACE-2 receivers on cell walls that SARS-Cov-2 uses to invade cells.
It depends how different the response to the vaccine vs the virus is. e.g. the vaccine immune response is based on the spike, while the virus could trigger an immune response based on some detail on the virus, but not the spike
I didn't say that. I said that the antibodies might behave differently (this is purely theoretical, I have no idea) when presented with a spike vs a spike attached to a corona. That different behavior might cause different long term effects. It might be that the virus causes the worse long term effects and an auto immune attack... In fact, I personally know someone who got an auto-immune induced arthritis from getting a virus infection in central America.
Considering that the original virus has this protein as well, I think getting the illness still will be worse. And in vaccine they can control amount of proteins produced. And they can check a lot of things before even hitting human trials, so risk should be minimal.
Our bodies ard entirely capable of doing that without external mRNA. Im also interested in potential side effects when we already have an autoimmune disorder.
The current recommendation is yes, you should get vaccinated.
(If we continue at the incredibly slow pace of vaccinations we're going, though, I wouldn't be surprised if experts start recommending people who have had Covid get lower priority. An expert recently shared that, at this rate, it will take ten years to get to herd immunity in the US. [1])
The problems so far are not related to the particular vaccines, but rather the lack of planning and money for said management. 10m doses have been distributed but only 2m given so far. States are really struggling due to lack of federal assistance in $$ and planning.
It's hard to know how much of the lag is A) holidays, B) reporting delays, C) logistics delays (allocation to the state isn't delivery to the point of care), vs D) ramping/administration delays.
I suspect many more doses have been given but not reported (B), and a lot more of the shortfall can be explained by A & C.
If that's true, we're going to be production limited very soon... though the decision to hold back more than half of the doses doesn't help.
Reaching phase 1B will help, too, because it will mean the opening of mass vaccination clinics, which can run in parallel to the remaining portion of 1A which is more targeted and logistically complicated. E.g. Santa Clara County Fairgrounds are set up for high throughput drive-through COVID testing and plans are to use the same infrastructure that can host massive numbers of cars and lanes to have massive numbers vaccinated and waiting out their 20 minute observation time. This site will be able to do thousands of doses per day-- >0.3% of the County's population per day-- alone, which exceeds the number of doses we can be expected to be allocated for quite some time.
Johnson and Johnson is the best hope for another near-term EUA, which could significantly improve vaccine supply in February.
The vaccine matters, as they have different storage requirements and dosing requirements. One of the vaccines requires that it be kept in a deep freeze, thawed before use, and everyone needs two doses. This is a logistically complicated process that takes much more time to deliver, and will therefore be slower.
The Oxford vaccine can be stored in a regular refrigerator, which drastically reduces infrastructure cost and makes it speedier to administer, since it doesn’t need to be carefully warmed to room temperature from subzero.
>Over 23,000 participants are being assessed following two doses of either a half-dose/full-dose regimen or a regimen of two full doses of AZD1222 or a comparator, meningococcal conjugate vaccine called MenACWY.
The placebo in the study was a meningitis vaccine that actually caused issues that halted the study and because astrazeneca's vaccine was deemed more effective than that, the vaccine was deemed a success.
In what way is that anywhere near a reasonable clinical study?
Their process was not reasonable. Which is why it was considered a failure and I believe they had to go back to the drawing board.
They will have to do a proper job, if they haven't already. With the other two vaccines already approved, national health boards will be in no rush to fast track it.
Not sure where you're getting your data, but it's incorrect.
It was not considered a failure. There have been some questions about what the best dosage and timing might be for the highest effectiveness, but I've heard the UK may approve it as early as tomorrow.
The USA may wait until the trial being run inside the USA is completed, but that has more to do with ensuring the vaccine is safe and works on their wide demographics than any concerns with how the UK and Brazil studies were done.
Having a placebo which has some degree of side effects is not insane, even though it caused problems here.
The vaccines have lots of side effects. If you give something with lots of side effects and compare it to a placebo with none, people have a good guess of what group they're in and behave differently. This is often considered more reasonable than comparing to a saline injection, and it's a reason why lots of drugs now are compared to e.g. ritalin-- something relatively benign with some side effect that feels like it is "doing something".
The half-dose/full-dose regimen was a mistake in a clinic administering the trial, though. A mistake that happened to look more effective than the overall vaccine population, which is a bit troublesome and a primary reason why AstraZeneca has problems now.
Now that we have effective COVID vaccines, we can run noninferiority trials-- e.g. comparing Moderna's vaccine to a potential new vaccine-- which get around a lot of the problems here.
Why is a correctly summarized answer, from a link to the CDC that directly states and answers the grandparents question, with source, being downvoted so heavily? Is there something I’m missing?
Maybe because this forum, as any other forum with significant impact, is influenced by third parties with commerical or political agendas through "bots" or cheap click workers.
Answer is yes but you are much lower priority than others, bottom of the priority stack. CDC made a huge mistake not clarifying this, and this mistake will make it take significantly longer for us to hit herd immunity.
There is very little chance you can catch it again if you already,and if you did it is likely to not be severe. But the immunity conferred by vaccines is often stronger and longer lasting from vaccines than from the disease itself. It's likely the case here based on preliminary numbers, but still not fully prove.
No. The answer isn't "yes". And you have linked to absolutely no studies to affirm whether this brand new vaccine is more effective than natural antibodies long-term. No such studies have been conducted.
Unless you've got an academic study with a clinical trial of two sets of populations one with natural antibodies, one with vaccination, and perhaps a third without it, you don't know and NYT doesn't know. The vaccine was rushed, showed maybe a 90% efficacy. There's not evidence of widespread Covid relapses after natural immunity is achieved. There's also literally no long term data on this vaccine, because it's brand new.
There are diseases that you can recover from without developing an immunity; tetanus is an example. The vaccine generates a much greater immune response than the actual disease.
Recent studies seem to indicate that tetanus vaccines are actually effective for at least 30 years. The UK and other countries don't recommend any booster shots for tetanus. Makes you wonder why we do in the US.
Which often is terrible advice that mostly serves to limit liability. Most medical doctors will not have a good, evidence-based answer to such questions.
Better reply: Search the internet for authoritative sources (e.g., official guidance of governmental institutions) or medical guidelines.
As this is the internet, medical questions are answered anecdotally by randoms, like me:
I got COVID back in March. I'd say I got medium sick. Worst few days of my life.
In the last 9 months I have been in close contact with people who have later also gotten ill, but I have not had any effects myself. So either I'm spreading it or I am immune (or both?). So there you go.
> Unlike DNA vaccines, mRNA vaccines do not have to cross the nuclear envelope, they pose no risk of genomic integration, and they work in both dividing and non-dividing cells.
This reads too much like a whitepaper / marketing material.
Of course mRNA doesn’t cross the nuclear envelope. It doesn’t mean that it’s not a potential danger to the cells, though.
I’m not anti-vax. But, I don’t want to gloss over the danger with vaccines that were fast-tracked and now will be given to a few billion people.
What could go wrong? Lots, but if we don’t take it, that could be much worse.
The "vaccine was rushed" thing is really all too common, and not at all a fair assessment of what happened. We got here a lot faster in many different ways.
1. Moderna only took 2 days to develop this COVID vaccine. [1] That was thanks to major advancements in vaccine development over many, many years. It wasn't just Moderna, other vaccine candidates were developed extra quick too thanks to advancements in science.
2. This vaccine was developed taking advantage of research done on very similar human coronaviruses over decades, starting from SARS in 2002.
3. Most diseases just aren't very prevalent in the population. For instance, if you created an ebola vaccine, there were a total of 14,000 cases globally between 2014 and 2016. Determining the efficacy would take years. On the other hand there have been 82 million cases of COVID since March. 19.2M in the US alone -- that's a prevalence of 5% (!!). It doesn't take long to prove the vaccine works when 1 in 20 people in the US have or have had COVID.
4. Most of the time human and animal trials are done back-to-back to reduce risk. With the government footing the bill and high confidence you can do them both at the same time.
All in all the result is a vaccine much faster but with all the usual rigor.
>All in all the result is a vaccine much faster but with all the usual rigor.
It's not all the usual rigor because vaccines can have side effects that only show up one or more years later, and it's literally impossible to test for such side effects without observing people who've taken the vaccine for at least a year afterwards.
Pretty much anything can have side effects that can only show up at a time interval longer than the measured time interval, that’s kind of the Nyquist theorem, the thing is, these kinds of vaccines have understood risk profiles. Yes literally anything can happen literally anytime, but we can guide our fears based on past experiences.
I would turn it around and say unless you have some reason why you would think that this particular vaccine design methodology will lead itself to having longer lead time side effects, a year of study is just fine.
Not so fast... fear / gauging safety isn’t strictly based on past experience, it’s also based on past inexperience.
The reason humans range from support of radical change to support of status quo when it comes to the known and unknown is a level of awareness that logic and experience can be defied for a better outcome in some situations.
Our level of scientific understanding during our lifetime may always be as that of those that believed that Earth was generally flat or those that had only just accepted that the Earth revolved around the Sun in what seemed to be a circle; both theories were and still may be held by some as truths, and perhaps to some benefit, but both are widely accepted to be incorrect now.
Fear is the mind-killer, but don’t confuse our innate questioning of what seems best and obvious to some for ignorant lack of acceptance of known truth. We can neither say there is no truth, nor that we know it, until we know it, and the jury is out about who knows it, except for those that believe in it being able to be known by someone.
At the current rate of infection, that would probably mean at least 80 million infected (more like 400-500 million in 1 year, since the infection rate now is much, much higher than that in February), and at least 1 million dead (again, more like 5-10 million due to the increased infection rate).
Even the worst vaccines we have had a defect/side effect rate much lower than that, I think the narcolepsy inducing one did it 1:10000 or even less. And it was narcolepsy, not death.
Bad vaccines seem to be better than Covid by several orders of magnitude...
As any biologist knows there are exceptions to almost all rules. It's not strictly correct there is zero risk of genomic integration, it's just very low. However there are some 4500 annotated retrocopies in the human genome, so spliced mRNA did cross back into the nucleus and was integrated in the genome at least this often in the human germline (with the help of retrotransposons).
Of course the likelihood of this happening, and then causing problems in vaccinated individuals are extremely small. Maybe even almost impossible as the mRNAs for the vaccines are heavily modified.
I think the incredibly historic accomplishments of these vaccines are unfortunately dulled quite a bit in this moment by the practical issues of how badly the US government and states are still bumbling the distribution of the vaccines.
I'm not talking the mundane details of the logistics of shipping, etc. getting those boxes out. That's well understood. I'm talking strategy of who gets vaccinated, how they find out, how they get in line to receive the vaccine. How government tracks and ensures that the population is getting to an effective level of immunity.
I have not seen a whiff of that information and management system being put in place. We're still random walking our way through this crisis. CVS has more information on the vaccination status of people in the country than the government does, for fuck's sake.
It's almost as if we're leaving it to everyone to figure it out themselves, or on a voluntary basis.
Do you know how you're supposed to get the vaccine? Has anyone contacted you or given you information? Have you seen any information on when you specifically are to sign up to receive the vaccine?
A more contagious/virulent variant of the virus was just detected in Colorado, today. And we're still letting a patchwork of counties figure it out as it comes.
Each state is handling the logistics themselves, but overall it seems that healthcare and state/government employees will have appointments set up through their employers. For the next several months, it's going to be elderly and then those whose jobs are deemed 'more important', which means communication will likely come from employers first for most people until general availability.
Employers are now responsible for ensuring the general public's health? Just for this initial stage? How frightening that is to realize. And for the rest of the population later?
A massive abdication of responsibility / competence by the government.
No, that is not at all what is happening. The government is deciding what occupations constitute early access to the vaccine. For now, they are prioritizing medical workers and government employees, especially those providing essential public services. The only possible way for that to work is through the employer themselves. This has always been the case, and has been publicly stated as such (frontline medical workers, assisted living workers, etc.). It was always going to be based on occupation initially. Once there's enough for general availability, individuals will likely be able to schedule vaccinations themselves or be contacted by their PCP to schedule one.
Just because you have not seen any communication does not mean it is not happening.
Delegation of operations outside of one's core competencies to others with proven track records of success seems smarter than reinventing the wheel from first principles. Employers, insurance companies and providers from med centers to corner pharmacies have a wealth of experience in delivering products into people's arms. Why let that go to waste?
Sure, but to OPs point, "overall it seems ... will have appointments set up..." isn't where we should be several weeks after the vaccine started shipping.
I asked myself the same question but in my country (in E.E.) I discovered the government has created an app for self registration in 3 stages - medical personnel first, then elderly and at risk people, then general population. I can't register yet. I assume US has something similar at the very least.
Your assumption is incorrect. There is no Federal government registration system in the US.
I'm in Australia and we are slow walking the process instead of using the equivalent of "emergency authorization". That's a risk that our Federal government is taking based on our very low case counts and infection rates.
Whether they roll it out efficiently between themselves and the individual state health authorities is yet to be seen.
Our Federal government has badly failed in its aged care response, which is its responsibility, while complaining loudly about states implementing border controls and other measures based on the economic impact.
Basically, governments that are run by inheritors of the Reaganite/Thatcherite "small government", "states rights" mindset are ignoring the fact that public health does not respect internal borders. This has occurred in the US, the UK, and, to a certain extent, in CA and AU.
I had the same questions myself, though not in the US but in Israel. We started vaccinations on the 20th and reached 500k yesterday, now up to 100k daily. (out of 8.8m population)
The media tried to cover all the how-s, when-s and what-if-s and did okay, and if you google for it you can find a government website with details about the vaccination campaign.
Finding out who's first in line was also easier than expected, that same info website has a link with a list of groups. The gist of it is: medical teams, elderly people, people aged >65, at-risk, then anyone who wants. It's a fairly long list but if you're interested see [1].
Re: signing up, at first it was via phone calls but later on HMOs (health orgs) made it possible to sign up via their apps. Once you sign up it's usually about a week. Some people somehow got an appointment for February but it was moved up to early January very quickly. E.g., my dad.
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[1]: From what I know and can find online now, after medical teams we vaccinated: nursing home caregivers & residents; then anyone over the age of 65 who signs up; then immunosuppressed people (implants etc.); then people with majorly reduced lung capacity; then personal caregivers. Those are all titled "first priority".
"Second priority" is: other risk groups such as diabetes, obesity, serious lung disease, hypertension, etc.; then high-exposure groups such as teachers, prisoners and guards, first responders. After that, anyone who wants to be vaccinated can sign up.
"Priority" also means "wave" at the moment; meaning until we vaccinated all (interested) people aged >65 I, a healthy person <30, can't get the vaccine.
That is a US specific problem. In fact, it's a US Federal government specific problem.
If you push responsibility from the Federal government to the states, each state has to work it out themselves. While the US is a republic of 50 states, there are some times where "states rights" should require them to work co-operatively to establish a standard for all 50 states.
The current administration, throughout the entire pandemic, has abdicated its responsibility to co-ordinate this. The fact that states were forming their own co-operative approaches (see NY/NJ/CT et al) demonstrates the issue.
Basically, the current administration castrated the CDC from performing its function, with political interference in what the CDC did and what the CDC announced.
The current vaccine distribution is effectively "wholesale" with 50 retailers and then the Federal government abdicates any further responsibility.
> For both products, adverse events elevated in the vaccine arm of the trial included ..., lymphadenopathy, nausea, erythema, Bell’s palsy and appendicitis.
If those are the bad side effects of the two vaccines that didn’t make the cut yet, what about the two that did?
> What is perhaps most exciting is the potential for mRNA as a rapid and generic platform for any desired immunogen(s). As upstream computational design and downstream processing and manufacture are standardized, custom work will mostly involve optimizing specific mRNA constructs to express efficiently in cells of interest.
It's always interesting to me when we shorten feedback loops like this. For example, could this significantly improve flu vaccines by allowing them to be more up-to-date? How much more quickly can we squash the next pandemic? Could we respond rapidly enough to help with common colds?
Yes, Moderna announced a few month ago that they are developing a few vaccine. But I'm personally much more excited about the personalized cancer vaccines that they are developing by designing the vaccine for the specific tumor and human genome.
As I understand it mRNA is one of the latter steps before a cell produces proteins that make up cells. The mRNA in the COVID vaccines is a precursor to immune system cells that can recognize COVID and deal with it. This represents a new way of training an immune system. The classical method is to put some dead or weakened disease cells in your body for your immune system to learn and practice defeating.
One method of approaching a cancer treatment might be to train the immune system to recognize cancer cells as something to be defeated. This on its own isn't new. What's new is the approach toward making a pipeline that can be tested for efficacy/safety/etc. The Bio Eats World podcast linked below has an explainer.
> Interesting parallel between the immune system and machine learning - they both need to train and curriculum training (vaccination) is more efficient.
It's almost like machine learning is a form of learning, right? :-D
> For example, could this significantly improve flu vaccines by allowing them to be more up-to-date? ... Could we respond rapidly enough to help with common colds?
As I understand it, the answer to both of these questions is likely to be "yes".
Can someone with a good understanding of virology and a passable understanding of code explain to me how mRNA vaccines are not a regex, and don't have the hazards of a regex?
What I mean is if the mRNA vaccine causes antigens that respond to a partial match of c-19 dna segments, which is how it is effective against even yet-to-be-developed spike proteins, isn't it necessarily associated with the hazards of fuzzy matching we have with regexes?
The antigens don't match on DNA segments. They match on proteins that the virus has on it. The mRNA sequence is specific to produce that very particular pattern. Not a wildcard.
And proteins have two major parts; the sequence of amino acids that they’re composed of, and how they’re folded. This folding detail is no small thing, as proteins don’t do the right thing when they’re folded wrong.
Actually, my understanding [1] is that the spike proteins are expected to come together to form a full spike, and that this is what the antibodies match off of.
So, even further from regex. The RNA gets turned into a sequence of amino acids, which folds in an extremely complex 3D shape, which bind together with two other proteins to form a large structure, the full shape of which is matched by antibodies.
I'm trying to even understand the question. Assuming you mean "regex" in the programming sense, then the two questions are of completely different domains, and assumming you can say anything about the "hazards" of one given your knowledge of the other sounds like the physicist who assumes that all problems can just be boiled down to some other problem he has a solution to.[1]
"If the mRNA vaccine causes the creation of antibodies which respond to a variety of spike proteins, how can we build confidence around the set of proteins which trigger and don't trigger an immune response, when the set of potential protein configurations is infinite"
I am not trying to mis-represent the problem by using a regex as an example, but trying to describe the "infinite set" aspect of the problem in a way that is understood by 90%+ of the people here.
> The new vaccines were 90 percent and 94.5 percent effective, said Mr. Paul, Republican of Kentucky and a trained ophthalmologist. And “naturally acquired” Covid-19 was 99.9982 percent effective, he claimed.
This is a good point, since you can't get COVID a second time if you're dead.
The issue is that you don't know whether you're going to be in the "recovered" group before you get COVID (which is why the vaccine is preferable, you get good immunity without the pesky dying).
Why would the vaccine only work on people that wouldn't die?
The vaccine trains the body to kill the virus (SARS-Cov-2) when it enters, not deal with the symptoms of the virus using the body to replicate (COVID-19).
my (laymans) model/hipothesis how this could work.
There are two groups of people. Latent antibody bombs (on slitghest signal antibodies go from zero to hero) and antibody deserts (where even at late stages of desease only low antibody counts are produced).
Those which easily make antibodies, kill off the virus quick enough to get significantly less side effects compared to the other group.
IF such model would hold, then it would be natural that antibody deserts dont produce much antibodies when reacting to vaccine, so there would be corellation between succeptible to covid mortality and vaccine innefectiveness.
In theory, yes. The trials clearly showed a reduction of bad cases too, so very unlikely. AFAIK, nobody died during the tests, so technically not tested.
It's ok. If you start to suffer from a persistent autoimmune reaction, I'm sure there's a therapeutic you can take for the rest of your life that only costs about 30k a month.
> The new nucleoside-modified mRNA vaccines are chemicals that have been almost fully disclosed. They incorporate a trinucleotide cap 1 analog ((m27,3′-O)Gppp(m2′-O)ApG), contain N1-methylpseudouridine instead of uridine, and encode an optimized (P2-mutated) full-length S glycoprotein encapsulated in lipid nanoparticles (LNPs) containing polyethylene glycol and cholesterol. The BNT162b2 LNP also contains (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) and 1,2-distearoyl-sn-glycero-3-phosphocholine, whereas Moderna’s LNP contains SM-102 (most likely heptadecan-9-yl 8-((2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino)octanoate) and 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG). ...
I'll disagree here. Imagine I tell you a white powder of pure molecular composition is made up of just four elements: carbon; hydrogen; nitrogen; and oxygen. Would you ingest it?
It could be strychnine (poison) or glycine (an amino acid). You have no way of knowing.
Likewise, the physiological effects lipid nanoparticles (LNPs) are still mysterious. First, the exact composition isn't known or even revealed in the FDA filing (thus the "most likely" above). Second, even given known composition, there's no way to know how large, how stable, or how aggregated these particles are or what any of that means.
The model for LNPs that gets most widely discussed is an artificial cell membrane. There's a water-filled center surrounded by a bilayer of lipid (grease). These particles may show variable sensitivity to degradation depending on how administered, composition, size, shape, trace impurities, and so on. For example, Moderna's vaccine contains cholesterol, presumably for the same reason our cells do - to modulate membrane fluidity. It's not clear just yet how persistent LNPs might be and what effects they might show, separate from the RNA payload.
Haven't the companies producing them been studying things like stability?
You say 'there's no way to know how large, how stable, or how aggregated these particles are or what any of that means', but they have been working with them for years.
Of course they could be lying or hiding information, but it seems like researching them is a way to know things about them.
> ... but they have been working with them for years.
True - in vitro and in limited human studies. But not at scale in human subjects. That's just this year. Studying this kind of thing is new as far as therapeutics go.
This is a good, detailed comment. It's so difficult to find good, detailed information, about the mechanics of this new vaccine. Thanks for writing it.
That's really outrageous analogy. Rearranging and interacting with droplets of PEG and cholsterol can't possiby have effect anywhere close to carefully and deliberatly arranging atoms into molecules in various ways to get different compounds.
Two U.S. pharmaceutical giants, Pfizer and Moderna, are in the final phase of coronavirus vaccine development, and Oxford University is expected to start large-scale human trials of its vaccine in the U.S. this month.
The initial numbers look awesome: Pfizer: 8/18,198 vaccine, 162/18,325 placebo; Moderna: 5/13,934 vaccine, 90/13,883 placebo for 7 and 14 days respectively after the second dose.
How long were the trials? I recall a famous drug that was given in the 70s and it produced birth malformations. Took years for doctors to realize the cause and ban its use in pregnant women. Is there a possibility of unforeseen consequences from using RNA? What if someone has for XYZ reason more reverse transcriptase than usual? Will his-her DNA be altered?
Of course there's a possibility. The problem with long-term effects is that if a problem takes 70 years to show up, then by definition we won't know about it for 70 years.
This applies not just to any drug you take, but also to the ingredients in the food you eat and the particles in the air we breath. We've come to such realizations before, and we will again.
But we also know for sure that COVID-19 is killing people right now.
The risk of long term effects is actually very small - almost insignificant. Long term effects tend to be an issue for drugs that are taken over the long term. With a vaccine that is only taken twice, the vaccine itself and its direct byproducts (ie the spike proteins) are only in the body for a limited period. After that it's only the immune response that remains. There's no realistic mechanism for a previously unseen effect to show up from it years down the line.
There is a small possibility that there could be detrimental effects to a fetus, which is why the vaccines are not currently recommended for pregnant women. It's not expected that there would be a negative effect; it just hasn't yet been tested. (Fortunately pregnancy is not a chronic condition, so people can still be vaccinated after giving birth.)
I'm not an expert myself, but I've done a lot of reading. I don't have a specific source at hand, but this is the consensus I've gotten from any interviews of vaccinologists or epidemiologists I've read or heard. Essentially that any side effects from vaccinations show up within a few weeks—that there just isn't a mechanism for them to appear years down the line if they haven't already been seen sooner, for the reason I described.
Now again it is possible that side effects could still be discovered in patients with complicating factors that weren't represented in the trials (like pregnancy or other known or unknown pre-existing conditions). Or just because the effects were too rare to show up significantly in the trials. But again these would be expected to show up quickly as widespread vaccination begins, as did the few severe allergic reactions that have occurred.
Of course as with anything, especially as charged an issue as vaccines, if one goes looking for it one can find plenty of purported evidence that long-term side-effects (by which I mean here side effects that don't show up until long after the vaccine is taken) are possible or even common. But the expert consensus based on the totality of evidence appears to be that this is not a serious concern.
There were also all the issues with the 1970s Swine Flu vaccine that turned out to not even be all that effective. 60 Minutes did a piece on it, and it's getting more and more difficult to search for on YouTube:
> it's getting more and more difficult to search for on YouTube
Just to be clear, since this sounds conspiratorial - it is most likely difficult to search because 60 minutes is a copyrighted show and they have an official YT channel but only carries segments of their episodes. So, I suspect it is quite difficult to find any full episode.
Could be, but several months ago it was very easy to find and now it's buried further and further down. Considering everything YouTube and Twitter have been doing over the past few months to control the narrative, it's also equally likely they're intentionally burying it.
I assume you're referring to the very slight increase in cases of GBS in people who had that particular swine flu vaccine? It's interesting to note that the CDC says that having the flu is more likely to cause GBS than getting the vaccine. Both of those risks are extremely slight.
My wife and I are trying to conceive and it's such a tough call whether or not she should get vaccinated. I try to read everything, even though I know the answer is "nobody knows." While we wait for more evidence we'll continue to quarantine and stay safe. We're hoping there's a bit more evidence by the time the vaccine is available to us.
I wish you weren’t downvoted, this is a valid, rational, and interesting question devoid of any kind of message or blanket statement like “all vaccines cause autism” or what have you.
The main difference is that the way the mRNA vaccine works is much better understood. Maybe better understood,on a molecular level, than many other medications.
There were human trials, but they skipped Longitudinal trials (long term effects) and they also didn't do challenge responses (exposing those people with the vaccine to COVID in a controlled manner), correct?
I find it fascinating how we submit batteries of tests to code as software engineers. Yet when it comes to our own health as a species, the rigor suddenly falls.
It's not lack of rigor, it's ethics. We don't want to intentionally expose people to something that might kill them. Instead, we perform a trial on a large group and allow them to naturally avoid or be exposed to the virus as they will. Then, with full mathematical and statistical rigor (the best kind of rigor) we determine whether the vaccine has a demonstrated benefit.
It'd be fine back when Jenner created the first vaccine over 185 years ago. There were no ethics boards back then. A lot of people died from snake oil treatments too.
We test code. We don't do destructive code tests in production.
Normal vaccine trials is like normal software testing. Challenge testing is like running dangerous tests in production. Its faster at detecting a problem than normal tests, but ultimately not needed and can blow up badly. The argument for doing it during covid is that time was of the essence and its faster than normal testing procedures. Instead we opted for the safer slower normal testing procedure.
They didn't just decide to "skip" long term effect studies. Long term effects can be studied only over a long term. No one wants to wait five or more years with the world in disarray.
Do longitudinal studies ever happen before a vaccine is released? Every longitudinal study I can find uses data from after a vaccine has been released to the general public. Stage 4 studies happen after the vaccine is in use by the general public.
“Even after the vaccine is approved and licensed, regulatory agencies stay involved, continuing to monitor production; inspecting manufacturing facilities; and testing vaccines for potency, safety and purity.
The FDA also monitors adverse events that may occur related to receiving the vaccine, including through its Vaccine Adverse Event Reporting System and Phase 4 clinical trials—optional studies pharmaceutical companies may be required to perform after a vaccine is licensed to continue to monitor safety and effectiveness.” [0]
So one of my takeaways from all of this is we cannot wait long enough based on current methods anymore. This virus is just one and it is likely to get worse. We need to invest now into large scale computer simulation of vaccines or things will become much worse. There is risk here, however I feel strongly that if we do need to move faster or today will become normal and that cannot become the normal! I read that most of the vacancies only took a few weeks for the scientist to create, however the current testing methods are why we are nearly 9 months to delivery. We as a society have to invest on new methods to move forward creation to delivery faster.
I am not claiming any expertise here - I majored in Biochemistry but never finished (moved to tech). I do have 14 doctors / geneticist / infection disease specialist in my family that share this view.
I've been wondering the same thing. How big of a computer would you need to accurately simulate an immune system? Or at least accurate enough to cut down on some of the tedious and time consuming work? Could something like this be built today with enough effort? I know nothing about immunology BTW.
The knowledge is not there to simulate the immune system in any useful way. Apart from that the main issue why it takes long to test vaccines are side effects. Checking for those would require simulating the whole body including various interactions with its environment.
> This virus is just one and it is likely to get worse. We need to invest now into large scale computer simulation of vaccines or things will become much worse.
This seems like a logical leap to me. Yes we need to do something to make us less open to viral threats, but you don’t present any evidence that improved computer simulations can be a useful tool in helping develop/test vaccines faster.
A simple search will yield months of reading. Just go to an HPC conference like SCinet (https://en.wikipedia.org/wiki/SCinet) and you will see besides energy, nukes and AI biological research is a key use of the computing power.
It's obvious that our methods of testing a vaccine have not caught up with our ability to produce a vaccine. But it does not seem clear or even plausible that we're ready to jump straight to full computer simulation. Our ability to predict protein folding via computer is pretty spotty, simulating the entire human immune system seems beyond our reach.
It also does not really seem to be supported by the evidence that things will never get back to normal if we don't do something radically different. We have a vaccine, there is no indication that we can't just distribute it and put this pandemic to bed.
I was talking with a doctor friend that oversees an ambulatory care group for the county, and they were able to allocate vaccines for the EMTs (first-responders).
This is a huge problem and not limited to anti-vaccination propaganda. The even bigger problem, climate change, suffers from the same problem. There is very loud propaganda out, especially on social media, which tries to deny the existance, throws doubt at attempts to limit it. Because it is spread by certain political forces, and this is an international problem. One which we have to address quickly, both now for the pandemic and long term (as in the next years) the climate change.
I am especially baffled by the anti-vaccination movement, as I grew up in a world where smallpox and polio had been basically erradicated due to vaccinations as were most of the typical childhood diseases. But where all the victims of those diseases were not forgotten yet. There was no doubt whatever to be vaccinated, I still can remember the polio vaccinations I got in school. And those were ridiculously risky compared to a modern Covid-19 vaccination. But overall the vaccinations saved so many more people than they harmed.
One can only hope that the next months will bring a change. On the one side, there will still be many deaths due to Covid-19, as the death spike follows 4-8 weeks after the infection count spike. On the other side, in two months the effect of the vaccinations should become very visible.
Scary things, as if the other known long term damages from Covid-19 were not enough. In any case, the vaccination should be magnitudes less risky than catching Covid-19. And as things are, there is a likelyhood that basically everyone would get infected at some time, if we don't put a hard stop to this.
I think you'd be surprised. Despite the ease of obtaining an EMT license in states in the US, it is relatively difficult to hire them [at the wage the market wants to pay, which is near minimum for commercial services]. You'd likely lose a substation portion of your service's staff by making that rule.
I think there's a substantial difference between wearing PPE and vaccination, both on the employer's side as well as the individual employee's perspectives. Mandating proper use of PPE can never have unintended side effects. No adult has ever died from improper use of an n95 face mask or nitrile gloves. The jury on the new vaccines is going to be out for a while on long term effects. It's not reasonable for an employer to require them yet.
Besides, that would spread the legal burden to the employer were something to go wrong.
The mRNA vaccines certainly look like a break-through in vaccine technology and with that technology now being used, it should be a good base for future vaccines. However I think the biggest change society in the west should take from Covid-19 is better disease fighting preparations. A lot of countries managed to avoid Covid-19 almost alltogether. All nations should learn from this. There are plenty of steps to be taken which could mostly prevent the catastrophic results of Covid-19 so the 9 months it took now to get an approved vaccine would have been an acceptable waiting time.
- reporting of the initial outbreak in Wuhan was too slow, but still, many countries acted in time.
- whenever a local outbreak of a similar new disease is reported, all countries should immideately go on an alert level, so that when the disease starts to spread, they can act immediately. If efficient reactions had been taken in January, a lot of things had been easier.
- of course watch international travel closely. If you close down flights, close down all travels. It doesn't make sense to ban flights from China, when the virus was coming to the US from Italy. It doesn't make sense to ban EU travellers but allow them to enter relaying via Turkey. Even better: don't ban flight travel, but test on arrival, make a short quarantine mandatory, that is more effective.
- lock down quickly and hard where neccessary, especial with local outbreaks
and the by far biggest elephant in the room:
- better hygene overall. Everyone should own proper masks, FFP2 masks should be stock piled by the government in generous amounts. Going forward, if you have symptoms of any infectious disease, wear a fucking mask! Even if it is the common cold, there is absolutely no justification to spread them to strangers. Even if it is not a deadly pandemic, infectious diseases could be reduced considerably by masks and hand sanitizing/washing. The yearly flu is deadly enough, there are no reasons to let it spread so freely.
I almost can't believe we were laughed and scoffed at for wearing a mask in March. Whether we had a respiratory infection or not. My biggest takeaway from the epidemic is that herd conformity is a ridiculously powerful force. Never underestimate it.
I was in Taiwan in 2013 and there it is absolutely common to wear a mask in public. Also, at the entrance of the 101 tower, there is a mall which had hand sanitizers at every entrance. Both things should become standard at all larger venues and would help a lot with all kind of infectious diseases.
I also hope, it becomes the new default to stay at home and work from there, if you have any symptoms. I don't know how many colds is picked up in the office in previous years.
I remember when our public health officials told us not to wear masks. Those same public health officials (Fauci) are now in interviews expressing disbelief and shock that people would choose not to wear masks - calling them science deniers even. My biggest takeaway from the epidemic is that government officials not only think it's ok to lie to the people in the name of the greater good, they also think gaslighting us is the appropriate way to deal with our skepticism towards them.
Yes, it was the one most prominent mistake in dealing with the pandemic, that there was no clear statement in favor of masks at the beginning. Only partially justifiable by the justified fear, that there would not be enough masks for medical personal.
All the involved should be harshly critisized for that.
However this should not be taken as an excuse to deny all good scientific information we have received and the right measures that have been recommended, especially the overly late committment to masks.
Which is a scandal for any nation, which considers itself industrial and advanced. But even plain and cheap medical masks have been shown in helping reducing infection spread and should be recommended. If everyone would consequently wear N95 masks only for a few weeks though, the pandemic should be greatly reduced in numbers.
They correctly estimated that compliance with encouragements would be very low (see e.g. current encouragements not to travel to see family at holidays).
If you tell people something that can keep them safe is available on Amazon for $25, all the encouragement in the world isn't going to keep that product from selling out.
That’s part of the communications problem about this pandemic, though: the masks aren’t all that effective at keeping you safe. They’re much more effective at keeping everyone around you safe.
You can look up the 60 minutes interview [1]. He said anyone sick should wear a mask, and they should be saved for sick and healthcare professionals.
I thought he also qualified his statement then that there was no evidence of wide scale community spread yet, but that might have been a different interview.
Regardless, it does highlight how hard it is to communicate with the public about a topic that is dynamic and fast changing.
Your assumption is everyone will follow that rules which is how we know now is not true. There always will be deniers and rule breakers, so even a very rigorous policy will not work as intended to stop the spread completely. Even not every country will follow those rules - look at today's Switzerland where ski resorts are open right now and full with tourists from neighboring countries.
No, I don't assume everyone will follow the rules. But if more people would follow the rules with a bit of discipline, things would be much better. As shown in Asian countries, which mostly don't have a Covid-19 problem. My list wasn't meant as preventing Covid-19 or similar diseases completely, but like things we can do to make the next pandemic a lesser problem in those months during which we wait for the vaccine. Not as a replacement for a vaccine, which always will the the one long-term solution to a pandemic.
One more thing towards rules: it really depends on a society agreeing. Like most societies agree that people should wear pants on the street, woman even shirts. There might be people breaking these rules, but overall society managed to make this a very infrequent thing.
> But if more people would follow the rules with a bit of discipline, things would be much better. As shown in Asian countries, which mostly don't have a Covid-19 problem
How do you know they have less case because people follow the rules ? I have been in Cambodia and Thailand and people don't really follow the rules there and there is barely any case
I don't claim to have all the answers, but these things could have been done and reduced the impact of the pandemic. How do I know this? Because it has been done by quite a few countries which did not have as much of a problem with the pandemic as the west had. Take Korea, Taiwan, New Sealand, Vietname, there are probably others. Japan also did much better than the west.
A few comments to the points you noted.
- Germany reacted at the end of February (I am from Germany), which was pretty late considering the international outbreaks, there were quite a few infections in Germany during February. But for the first wave, Germany reacted just in time to avoid a lot of deaths (<10k), but completely failed at preventing the 2nd wave. But even the first lockdown might have been prevented by acting in early february. Carnival was allowed to take place and it was one major outbreak, the other was Ischg in Austria.
- Borders to France and Swizerland had been eventually closed. When it was pretty late. But I was more referring to the US reaction, which banned travel from China only and much later (to late) from Europe, which is still in place, but allow travel via Turkey, which is what all Europeans going to the US are using.
- If you handle local outbreaks quickly, you can get infections down to 0 in the affected region.
- There is plenty of evidence, that masks reduce the transmission of Covid-19, but I was also speaking in a general sense, as I said "any infectious disease". There is no need to spread the cold or flu as quickly as we used to do. As far as I know, since the pandemic, the flu numbers are down a lot, as hygene works.
> - If you handle local outbreaks quickly, you can get infections down to 0 in the affected region.
This is not true for a country like Germany, you would have to hard lockdown for some time and close all borders, and then verify any person who cross the border, and free move in Europe won't make that possible unless all EU countries do it. If you are an island things gets easier in that matter.
The ONLY country which were able to go to zero after a big outbreak is China
Yes, after a big outbreak. I was talking about the time, when there were a few single cases. In Munich, this worked once, in Heinsberg, it mostly worked, but there the spread was larger due to the infected attending an event. And a lot of cases in Germany were caused by one person in Ischgl which acted completely foolish.
You're ignoring the biggest high level problem in the US: leadership that ignores science. If we had political leaders that made their decisions based on science and research we wouldn't be in such a big mess. Without that leadership the changes you listed won't happen.
The problem I see with your recommendations are that they're highly COVID specific. In hindsight so much of this seems obvious - masks, effective targetted lockdowns, restrict travel, stockpiling medical equipment, etc. These are commonsense observations clear to observers in January 2020 - but they come with very considerable costs. The effectiveness of each of these measures is also nebulous, and how much we weigh them has also changed. How effective any of these measures will be against the next pandemic is also unclear. Next time it may not be a respiratory illness.
There are various options for RNA polymerases commonly used in vitro [1], generally the error rate is considered to be "pretty low", something like 1 in 10k. An error will also have to result in a change of amino acid, which less likely due to the redundancy of the code. So any error mRNA will probably only have one amino acid changed. This could cause the resulting spike protein to aquire some new characteristic, but it's not very likely I would guess.
Also, in the clinical trials they test the actual produced vaccine, with all errors included.
Thinking about this some more, there may even be an advantage: The virus also mutates, so some error mRNAs may actually confer additional immunity to future or current virus strains. In reality there are probably way to few errors for this to make a difference...
It's highly redundant when there are 2 strands, as is the case with DNA.
RNA has a tendency to accumulate mutations quickly, as evidenced by the many hundreds of variants of SARS-CoV-2 that have already been sequenced (and that's with only ~30,000 bases).
You have to keep in mind that there are lots of individual mRNA molecules in each vaccine. So an error won't affect all of them, but only a tiny fraction of the total vaccine. The error rate overall should be similar or lower than the error rate for any other mRNA and the viral RNA. The mRNA in the vaccine is not produced chemically, but with an enzyme (polymerase) like mRNA in cells.
Allergic reactions are like shark attacks. Extremely rare but get tons of press coverage, making them seem more common than they are.
All vaccines have a risk of allergic reactions. This is why you're supposed to be monitored for at least 10 minutes after the injection. This is especially important for people who have a history of such reactions to vaccines.
None of the 18860 participants of the Phase 2/3 trial reported allergic reactions after either dose of the vaccine [1]. Over the entire duration of the study, one member of the treatement group suffered an anaphylactic reaction and one member of the placebo group an anaphylactic shock [2]. There is no hint that this particular vaccine is more likely to trigger allergic reactions than any other kind of medication.
And unless you are in a high risk group, there will be millions more that will have gotten the vaccine before you even have the chance to make that choice.
How do they classify something like this as safe for the long term if long term experiments are not conducted? Is there any substitute for time trials for drugs other than these new vaccines? These are the questions my relatives are asking me and my answers are I don't know, I don't. The scientific community needs to do a better job of communication. Why are we confident that a trial of only three months is sufficient when the only efficacy test for long term effects is long term trials?
They are not classified as safe for long term use - they're still not approved. They're been cleared by an EUA for emergency use. We don't know how safe they are for long term use yet, since those trails are still ongoing - Pfizer's 3rd Phase trials run till the summer of 2021, and Moderna's trial runs till mid 2022. We'll have more concrete answers then.
That's why an Emergency Use Authorization is just that - there's an emergency. The FDA is well aware that long term safety is still unclear, but given the circumstances, the risks posed by vaccination for the general public are outweighed by the benefits.
The only problem is from a communication with the public is that as many people has physically possible will be vaccinated. How is this "emergency" approval any different then a general approval if the end result of the same?
" but given the circumstances, the risks posed by vaccination for the general public are outweighed by the benefits. "
That's the problem, we don't. We don't know what the risk is long term, it is unknown. It is illogical to say that an completely unknown risk has any logical comparison.
While we don't have an exact handle on the risks posed by the vaccine long term, we do have reasonable bounds on what they may be. For example, it's entirely possible 0.05 - 0.6% of people who receive the vaccines develop long term severe negative outcomes. Perhaps that number is 3% - we don't know, but more unlikely. We can be fairly certain that number isn't as high as 40%. We don't have all the numbers, but we have reasonable assumptions - these are non integrative mRNAs that have a very short lifespan inside the body, so long term effects other than immunity are not expected. Of course, there is uncertainty in everything.
This is more uncertainty than the FDA would accept in the usual course of events - but this is an unusual time. The FDA has no adequate, approved, and available alternatives to the emergency authorization when faced with the pandemic. The investigational vaccine appears to be safe and effective against COVID-19 for the general population. Yes, the vaccine poses some unknown risks, but they are very likely vanishingly smaller than the very present health risks posed by the pandemic. For any given individual, they're much more likely to suffer negative health outcomes within the next 5 years from COVID than from the vaccine. Nobody is stating that risk to be zero. But that also doesn't mean "the risk is completely unknown so why even bother?"
How is the emergency authorization any different from an approval? If tomorrow an effective treatment for COVID-19 were to be approved or the pandemic ends, the EUA for the vaccine would be rescinded. Pfizer/Moderna must also track any adverse reactions more closely, and report them to the FDA on an ongoing basis. They also cannot sell them to private players - they're being provided to the FDA & their authorized parties. The vaccines are not licensed for COVID or any other use.
Thanks, you gave more information than is being publicly disseminated. I'd like to see CDC publications on the long term bounds cited. Random people on the Internet is not compelling. Also, mRNA vaccines have been ongoing for years. We need better communication on why now other than we're really smart, now, and the gov. spent billions. If that is all it took we'd have cured cancer long ago.
How does the immune system keep a memory of what every single non-foreign protein looks like so that it can recognize foreign ones? That's the most amazing thing here, to me.
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[ 4.7 ms ] story [ 261 ms ] threadWe also don’t fully understand what causes autoimmune disease, but various environmental causes have been explored including bacterial and viral infections. Presumably if a viral infection could trigger an autoimmune response in certain genetically predisposed groups, then so could a vaccine designed to mimic a virus.
Unfortunately the incentives in our medical system are not designed to find cures for autoimmune diseases, although they are very much incentivized for palliative care, so progress has been painfully slow in understanding the deeper complexities of the immune system.
This is true. Some of the extremely rare auto-immune issues that have impacted people who have been vaccinated for specific flu viruses in, IIRC, 1976 and 2009, were thought to occur at even higher rates and severity with people who contracted the virus. So, vaccination might impact you, but likely worse the the virus itself due to the greater amount of virus in your system.
I am not a scientist, but I would expect that the mRNA vaccines would have less of a chance of having an auto-immune reaction since they contain only one of the many proteins contained in the actual virus.
There exist even special medicine to account for genetic differences in Black people: https://en.wikipedia.org/wiki/Isosorbide_dinitrate/hydralazi...
To GP’s point, lack of diversity in clinical trials can result in medicines that vary in efficacy and safety in the broader population. The ability to customize a therapy to an individual would help reduce the impact of this issue.
1000 years ago you probably could have said that indigenous subsaharan Africans and Americans are different subspecies of homo sapiens simply because one group has darker brown skin and lives in Africa, and one has lighter brown skin and lives in the Americas (phenotype difference + range difference is all it takes). But today the "native range" of every ethnic group is essentially global due to airplanes and immigration, so you'd probably say we're all one subspecies. But either way, the label "subspecies" conveys far less information than people sometimes assign it.
This is the angle that, for me, is suppressing my innate concern for a widescale and rapid application of a brand new immunological therapy. It's extremely targeted and feels like the future. I can imagine a day where the FDA approves the process rather than the instance of mRNA-based therapies, allowing for highly personalized treatment.
This was recently noted in a AMA by virus experts on reddit.
Sure, but aren't the proteins produced by the vaccine virtually identical to the ones produced by the actual virus?
If so, the calculus looks like this:
1) Take the vaccine and accept the (unknown, but apparently quite small) probability that something in your body will react very negatively to the generated viral proteins.
2) Get the virus, accept the probability (also unknown, but the same as in 1) that something in your body will react very negatively to the viral proteins, plus accept the additional risk of being infected by the actual virus.
I guess the third possibility would be to refuse the vaccine and gamble that you won't get the virus, either.
If that's generally true, the difference here would be that the part of the spike protein topology that is typically bound to other proteins in an actual infection would be accessible to the immune system in the case of a vaccination. I think that is where the differential risk could occur with a vaccination that wouldn't occur with an actual infection (however small that might be).
In my daughter's case, something happened when she was about 14 years old that caused her body to determine that the beta cells in her pancreas were invaders and have to die, so I'm just tuned into this kind of possible side effect.
If the virus is destroyed and released into the extracellular environment, its proteins can dissociate and are further fragmented and processed by the immune system. What’s usually presented to T cells are small antigen pieces as opposed to the whole virus/protein.
Virus takes over the cell, makes the cell to manufacture components of the virus and to assemble viruses, until this disrupts the cell so bad that the cell dies and typically bursts. Surely at this point, not only assembled viruses, but also components at different stages of production, are released?
https://en.wikipedia.org/wiki/Introduction_to_viruses#Life-c...
https://vimeo.com/260291607
OT, but what does this mean or refer to? I'm curious :)
Corny but fun, they had a few good ones.
I was wrong, its the nucleocapsid protein, not the membrane one, but that's even weirder as the N protein is only found inside the virus particle..
I think the answer to this questions would be nice to have.
"Several vaccine candidates are expected to induce the formation of humoral antibodies against spike proteins of SARS-CoV-2. Syncytin-1 (see Gallaher, B., “Response to nCoV2019 Against Backdrop of Endogenous Retroviruses” - http://virological.org/t/response-to-ncov2019- against-backdrop-of-endogenous-retroviruses/396), which is derived from human endogenous retroviruses (HERV) and is responsible for the development of a placenta in mammals and humans and is therefore an essential prerequisite for a successful pregnancy, is also found in homologous form in the spike proteins of SARS viruses. There is no indication whether antibodies against spike proteins of SARS viruses would also act like anti-Syncytin-1 antibodies. However, if this were to be the case this would then also prevent the formation of a placenta which would result in vaccinated women essentially becoming infertile. To my knowledge, Pfizer/BioNTech has yet to release any samples of written materials provided to patients, so it is unclear what, if any, information regarding (potential) fertility-specific risks caused by antibodies is included."
> Jacob Yount, an associate professor of the department of microbial infection and immunity at Ohio State University, College of Medicine, has studied the syncytin proteins as well as SARS-CoV-2. Yount said the COVID vaccines do not contain syncytin-1 protein or mRNA encoding syncytin-1, and thus there is no reason to think that an immune response against syncytin-1 would be developed.
> “We don’t see infertility with the flu vaccine and that is also targeting a viral fusion protein in a similar way that the spike is a viral fusion protein of the coronavirus,” he said.
https://apnews.com/article/fact-checking-9856420671
This professor doesn't know about how much of the sequence is copied. He doesn't know the widespread affect of mRNA vaccines because we're in new territory here and it's possible that the risk of autoimmune responses is higher with such vaccines. He should know better than to equate mRNA vaccines with more traditional vaccines.
With every vaccine, a small percentage of people suffer adverse and autoimmune effects.
As that professor well knows, we're NOT discussing possibility (with that billions of people lined up, it's all but inevitable). Instead, we're discussing PROBABILITY that it will happen and how many people will be adversely affected.
I'm not saying the vaccine is bad or that people should freak out and not get vaccinated (even some vaccines with high complication rates have historically been much more helpful than harmful). I'm pointing out that while the intentions of the professor may be good, they're definitely not speaking the absolute truth and aren't actually in a position to know all the actual details about the vaccine.
My understanding is that, yes, the proteins are similar, but not the same, and that a similar protein also exists in influenza which does not cause infertility when targeted by our antibodies. I assume this doesn't mean that it couldn't cause infertility in the case of a COVID-19 vaccine, but it would suggest it's perhaps unlikely.
Is there any reason to believe an mRNA vaccine would be anymore likely to cause our antibodies to target the syncytin-1 spike protein as opposed to a more traditional vaccine?
I do agree with your point that it's more a question of the probability of side effects than a possibility. This is something that's bothered me about the attacks on those who are hesitant on the safety of these vaccines. Although I'm sure there's a very low risk that someone will suffer any adverse effects from these vaccines there is almost certainly going to be some cases of adverse side effects, so in the interest of public trust in the COVID-19 vaccines and all future vaccines we should be ensuring the public understand the risks fully and not attacking anyone for asking questions or expressing doubts, because if it does turn out that some of those doubts did indeed hold merit then no one will trust a word the media or professors have to say on this in the future.
―https://en.wikipedia.org/wiki/Cross-reactivity#Applications_...
EDIT: The mRNA vaccines are obviously not therapeutic antibodies, but they probably checked for cross-reactivity of the engineered spike protein as well as the generated antibodies using similar methods. I’m not 100% sure, though.
There is a study[0] showing cross-reactivity between SARS-CoV-2 antibodies and other human tissues, thus predisposing the host to autoimmune diseases. This should apply even more so to any vaccine since vaccines produce a more robust immune response.
Phase 2/3 of Pfizer-BioNTech did, however, include people with autoimmune diseases [1]. Other vaccine trials did not, as far as I am aware. This does not really shine a light on pre-disposition to an autoimmune disease 6-9-12 mo down the road.
Reading this comment again before I post made me realize it sounds very gloomy, so I feel obliged to say I'll be getting whatever vaccine I can get my hands on at the soonest possible date.
[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246018/#__ffn_...
[1] https://www.fda.gov/media/144245/download
> There is a study[0] showing cross-reactivity between SARS-CoV-2 antibodies and other human tissues, thus predisposing the host to autoimmune diseases. This should apply even more so to any vaccine since vaccines produce a more robust immune response.
Since the antibody tested in the study was a commercial, monoclonal one, this is somewhat hard to assess. But I think you’re right given what they found in the blood tests.
> This does not really shine a light on pre-disposition to an autoimmune disease 6-9-12 mo down the road.
Autoimmune reactions should happen in the short run, right?
I believe Pandermix took 6 months for narcolepsy to develop.
the onset judged by "first contact to health care" was much earlier.
The narcolepsy issue was never going to be uncovered before it was rolled out large scale.
It is at this point that I remind myself of all the other dangerous things that I do: driving, motorcycling, rock climbing, skiing, etc.
The risk of long term side effects is worth the benefit of spinning up the global economy again.
Here is a study of the effects - https://www.nejm.org/doi/full/10.1056/NEJMoa2024671.
It doesn't directly address your question, but it does show how the vaccine performs to control (labeled pbs) in terms of viral load and immune system activity when challenged with a dose of the virus.
The two shots have nothing to do with mRNA stability, they improve immunity, as in any other vaccine given in two or three shots.
The very end of mRNA is polyadenylated. This is a fancy way of saying it ends on a lot of AAAAAAAAAAAAAAAAAAA. Even mRNA has had enough of 2020 it appears.
mRNA can be reused many times, but as this happens, it also loses some of the A’s at the end. Once the A’s run out, the mRNA is no longer functional and gets discarded. In this way, the ‘poly-A’ tail is protection from degradation.
Studies have been done to find out what the optimal number of A’s at the end is for mRNA vaccines. I read in the open literature that this peaked at 120 or so.
The BNT162b2 vaccine ends with:
UAGCAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAGCAUAU GACUAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAA
This is 30 A’s, then a “10 nucleotide linker” (GCAUAUGACU), followed by another 70 A’s.
[0]: https://news.ycombinator.com/item?id=25538820
The mRNA isn't intended to be copied in the body. Once the dose is used up there should be no more spike proteins created.
Reading https://theconversation.com/what-is-the-ace2-receptor-how-is...
there is a section that explains the difference between ACE-1 inhibitors (like in ramipril etc) and ACE-2 inhibitors.
Wikipedia has the layman's details of the RAAS system:
https://en.wikipedia.org/wiki/Renin%E2%80%93angiotensin_syst...
Are you saying introducing other markers as well would make the presence of the spike protein less risky? Why would that be the case?
(If we continue at the incredibly slow pace of vaccinations we're going, though, I wouldn't be surprised if experts start recommending people who have had Covid get lower priority. An expert recently shared that, at this rate, it will take ten years to get to herd immunity in the US. [1])
1. https://twitter.com/DrLeanaWen/status/1343920976854196225
I suspect many more doses have been given but not reported (B), and a lot more of the shortfall can be explained by A & C.
If that's true, we're going to be production limited very soon... though the decision to hold back more than half of the doses doesn't help.
Reaching phase 1B will help, too, because it will mean the opening of mass vaccination clinics, which can run in parallel to the remaining portion of 1A which is more targeted and logistically complicated. E.g. Santa Clara County Fairgrounds are set up for high throughput drive-through COVID testing and plans are to use the same infrastructure that can host massive numbers of cars and lanes to have massive numbers vaccinated and waiting out their 20 minute observation time. This site will be able to do thousands of doses per day-- >0.3% of the County's population per day-- alone, which exceeds the number of doses we can be expected to be allocated for quite some time.
Johnson and Johnson is the best hope for another near-term EUA, which could significantly improve vaccine supply in February.
The Oxford vaccine can be stored in a regular refrigerator, which drastically reduces infrastructure cost and makes it speedier to administer, since it doesn’t need to be carefully warmed to room temperature from subzero.
Oh, and it’s cheaper. That matters.
There's no guarantee things would be going any faster, but if anyone can walk into a pharmacy and get a shot it seems like it would speed up a bit.
But how is astrazeneca's methodology reasonable?
https://www.astrazeneca.com/media-centre/press-releases/2020...
>Over 23,000 participants are being assessed following two doses of either a half-dose/full-dose regimen or a regimen of two full doses of AZD1222 or a comparator, meningococcal conjugate vaccine called MenACWY.
The placebo in the study was a meningitis vaccine that actually caused issues that halted the study and because astrazeneca's vaccine was deemed more effective than that, the vaccine was deemed a success.
In what way is that anywhere near a reasonable clinical study?
They will have to do a proper job, if they haven't already. With the other two vaccines already approved, national health boards will be in no rush to fast track it.
It was not considered a failure. There have been some questions about what the best dosage and timing might be for the highest effectiveness, but I've heard the UK may approve it as early as tomorrow.
The USA may wait until the trial being run inside the USA is completed, but that has more to do with ensuring the vaccine is safe and works on their wide demographics than any concerns with how the UK and Brazil studies were done.
https://news.ycombinator.com/item?id=25549454
The vaccines have lots of side effects. If you give something with lots of side effects and compare it to a placebo with none, people have a good guess of what group they're in and behave differently. This is often considered more reasonable than comparing to a saline injection, and it's a reason why lots of drugs now are compared to e.g. ritalin-- something relatively benign with some side effect that feels like it is "doing something".
The half-dose/full-dose regimen was a mistake in a clinic administering the trial, though. A mistake that happened to look more effective than the overall vaccine population, which is a bit troublesome and a primary reason why AstraZeneca has problems now.
Now that we have effective COVID vaccines, we can run noninferiority trials-- e.g. comparing Moderna's vaccine to a potential new vaccine-- which get around a lot of the problems here.
More on that here: https://news.ycombinator.com/item?id=25548342
Edit: And this honest question asking why is too?
There is very little chance you can catch it again if you already,and if you did it is likely to not be severe. But the immunity conferred by vaccines is often stronger and longer lasting from vaccines than from the disease itself. It's likely the case here based on preliminary numbers, but still not fully prove.
You very likely have good enough immunity to wait. Let someone unprotected get the shot.
2) The running theory is that an immunological response is primed by a first infection, so you'll probably benefit little
https://watermark.silverchair.com/ciw066.pdf?token=AQECAHi20...
Better reply: Search the internet for authoritative sources (e.g., official guidance of governmental institutions) or medical guidelines.
https://tkp.at/2020/12/12/meduni-innsbruck-immunitaet-durch-... (German)
This reads too much like a whitepaper / marketing material.
Of course mRNA doesn’t cross the nuclear envelope. It doesn’t mean that it’s not a potential danger to the cells, though.
I’m not anti-vax. But, I don’t want to gloss over the danger with vaccines that were fast-tracked and now will be given to a few billion people.
What could go wrong? Lots, but if we don’t take it, that could be much worse.
It's not just marketing: there was a COVID DNA vaccine competitor and it lost.
1. Moderna only took 2 days to develop this COVID vaccine. [1] That was thanks to major advancements in vaccine development over many, many years. It wasn't just Moderna, other vaccine candidates were developed extra quick too thanks to advancements in science.
2. This vaccine was developed taking advantage of research done on very similar human coronaviruses over decades, starting from SARS in 2002.
3. Most diseases just aren't very prevalent in the population. For instance, if you created an ebola vaccine, there were a total of 14,000 cases globally between 2014 and 2016. Determining the efficacy would take years. On the other hand there have been 82 million cases of COVID since March. 19.2M in the US alone -- that's a prevalence of 5% (!!). It doesn't take long to prove the vaccine works when 1 in 20 people in the US have or have had COVID.
4. Most of the time human and animal trials are done back-to-back to reduce risk. With the government footing the bill and high confidence you can do them both at the same time.
All in all the result is a vaccine much faster but with all the usual rigor.
[1] https://www.businessinsider.com/moderna-designed-coronavirus...
It's not all the usual rigor because vaccines can have side effects that only show up one or more years later, and it's literally impossible to test for such side effects without observing people who've taken the vaccine for at least a year afterwards.
I would turn it around and say unless you have some reason why you would think that this particular vaccine design methodology will lead itself to having longer lead time side effects, a year of study is just fine.
Excellent.
The reason humans range from support of radical change to support of status quo when it comes to the known and unknown is a level of awareness that logic and experience can be defied for a better outcome in some situations.
Our level of scientific understanding during our lifetime may always be as that of those that believed that Earth was generally flat or those that had only just accepted that the Earth revolved around the Sun in what seemed to be a circle; both theories were and still may be held by some as truths, and perhaps to some benefit, but both are widely accepted to be incorrect now.
Fear is the mind-killer, but don’t confuse our innate questioning of what seems best and obvious to some for ignorant lack of acceptance of known truth. We can neither say there is no truth, nor that we know it, until we know it, and the jury is out about who knows it, except for those that believe in it being able to be known by someone.
Even the worst vaccines we have had a defect/side effect rate much lower than that, I think the narcolepsy inducing one did it 1:10000 or even less. And it was narcolepsy, not death.
Bad vaccines seem to be better than Covid by several orders of magnitude...
Of course the likelihood of this happening, and then causing problems in vaccinated individuals are extremely small. Maybe even almost impossible as the mRNAs for the vaccines are heavily modified.
I'm not talking the mundane details of the logistics of shipping, etc. getting those boxes out. That's well understood. I'm talking strategy of who gets vaccinated, how they find out, how they get in line to receive the vaccine. How government tracks and ensures that the population is getting to an effective level of immunity.
I have not seen a whiff of that information and management system being put in place. We're still random walking our way through this crisis. CVS has more information on the vaccination status of people in the country than the government does, for fuck's sake.
It's almost as if we're leaving it to everyone to figure it out themselves, or on a voluntary basis.
Do you know how you're supposed to get the vaccine? Has anyone contacted you or given you information? Have you seen any information on when you specifically are to sign up to receive the vaccine?
A more contagious/virulent variant of the virus was just detected in Colorado, today. And we're still letting a patchwork of counties figure it out as it comes.
A massive abdication of responsibility / competence by the government.
Just because you have not seen any communication does not mean it is not happening.
In the first stage, yeah, because the employees are mainly healthcare workers.
I'm in Australia and we are slow walking the process instead of using the equivalent of "emergency authorization". That's a risk that our Federal government is taking based on our very low case counts and infection rates.
Whether they roll it out efficiently between themselves and the individual state health authorities is yet to be seen.
Our Federal government has badly failed in its aged care response, which is its responsibility, while complaining loudly about states implementing border controls and other measures based on the economic impact.
Basically, governments that are run by inheritors of the Reaganite/Thatcherite "small government", "states rights" mindset are ignoring the fact that public health does not respect internal borders. This has occurred in the US, the UK, and, to a certain extent, in CA and AU.
The media tried to cover all the how-s, when-s and what-if-s and did okay, and if you google for it you can find a government website with details about the vaccination campaign.
Finding out who's first in line was also easier than expected, that same info website has a link with a list of groups. The gist of it is: medical teams, elderly people, people aged >65, at-risk, then anyone who wants. It's a fairly long list but if you're interested see [1].
Re: signing up, at first it was via phone calls but later on HMOs (health orgs) made it possible to sign up via their apps. Once you sign up it's usually about a week. Some people somehow got an appointment for February but it was moved up to early January very quickly. E.g., my dad.
--
[1]: From what I know and can find online now, after medical teams we vaccinated: nursing home caregivers & residents; then anyone over the age of 65 who signs up; then immunosuppressed people (implants etc.); then people with majorly reduced lung capacity; then personal caregivers. Those are all titled "first priority".
"Second priority" is: other risk groups such as diabetes, obesity, serious lung disease, hypertension, etc.; then high-exposure groups such as teachers, prisoners and guards, first responders. After that, anyone who wants to be vaccinated can sign up.
"Priority" also means "wave" at the moment; meaning until we vaccinated all (interested) people aged >65 I, a healthy person <30, can't get the vaccine.
If you push responsibility from the Federal government to the states, each state has to work it out themselves. While the US is a republic of 50 states, there are some times where "states rights" should require them to work co-operatively to establish a standard for all 50 states.
The current administration, throughout the entire pandemic, has abdicated its responsibility to co-ordinate this. The fact that states were forming their own co-operative approaches (see NY/NJ/CT et al) demonstrates the issue.
Basically, the current administration castrated the CDC from performing its function, with political interference in what the CDC did and what the CDC announced.
The current vaccine distribution is effectively "wholesale" with 50 retailers and then the Federal government abdicates any further responsibility.
afaik if you don't know or haven't been contacted you're not on the list yet. You know it's your turn when they tell you it is.
> A more contagious/virulent variant of the virus was just detected in Colorado, today
There are 10 articles a day about new "mutant and more virulent strains" around the world which aren't supported by any evidences
If those are the bad side effects of the two vaccines that didn’t make the cut yet, what about the two that did?
> What is perhaps most exciting is the potential for mRNA as a rapid and generic platform for any desired immunogen(s). As upstream computational design and downstream processing and manufacture are standardized, custom work will mostly involve optimizing specific mRNA constructs to express efficiently in cells of interest.
It's always interesting to me when we shorten feedback loops like this. For example, could this significantly improve flu vaccines by allowing them to be more up-to-date? How much more quickly can we squash the next pandemic? Could we respond rapidly enough to help with common colds?
One method of approaching a cancer treatment might be to train the immune system to recognize cancer cells as something to be defeated. This on its own isn't new. What's new is the approach toward making a pipeline that can be tested for efficacy/safety/etc. The Bio Eats World podcast linked below has an explainer.
https://en.wikipedia.org/wiki/Messenger_RNA
https://bio-eats-world.simplecast.com/episodes/moderna-covid...
Interesting parallel between the immune system and machine learning - they both need to train and curriculum training (vaccination) is more efficient.
It's almost like machine learning is a form of learning, right? :-D
As I understand it, the answer to both of these questions is likely to be "yes".
https://www.theguardian.com/world/2020/dec/05/team-behind-ox...
What I mean is if the mRNA vaccine causes antigens that respond to a partial match of c-19 dna segments, which is how it is effective against even yet-to-be-developed spike proteins, isn't it necessarily associated with the hazards of fuzzy matching we have with regexes?
They have no way to access the underlying DNA.
The BioNtech-Vaccine accounts for this afaik, to prevent the spike-proteins from clumping.
So, even further from regex. The RNA gets turned into a sequence of amino acids, which folds in an extremely complex 3D shape, which bind together with two other proteins to form a large structure, the full shape of which is matched by antibodies.
1. https://www.nytimes.com/interactive/2020/health/pfizer-biont...
The vaccine is in no way shape or form a "regex."
1. https://xkcd.com/793/
"If the mRNA vaccine causes the creation of antibodies which respond to a variety of spike proteins, how can we build confidence around the set of proteins which trigger and don't trigger an immune response, when the set of potential protein configurations is infinite"
I am not trying to mis-represent the problem by using a regex as an example, but trying to describe the "infinite set" aspect of the problem in a way that is understood by 90%+ of the people here.
This is a good point, since you can't get COVID a second time if you're dead.
Do they test for vaccine innefectiveness corelation with virus lethality and/or complications?
The vaccine trains the body to kill the virus (SARS-Cov-2) when it enters, not deal with the symptoms of the virus using the body to replicate (COVID-19).
Vaccines stop infection.
Therapeutics stop disease.
The map is not the territory.
There are two groups of people. Latent antibody bombs (on slitghest signal antibodies go from zero to hero) and antibody deserts (where even at late stages of desease only low antibody counts are produced). Those which easily make antibodies, kill off the virus quick enough to get significantly less side effects compared to the other group.
IF such model would hold, then it would be natural that antibody deserts dont produce much antibodies when reacting to vaccine, so there would be corellation between succeptible to covid mortality and vaccine innefectiveness.
I wonder who's down voting this and why.
I'll disagree here. Imagine I tell you a white powder of pure molecular composition is made up of just four elements: carbon; hydrogen; nitrogen; and oxygen. Would you ingest it?
It could be strychnine (poison) or glycine (an amino acid). You have no way of knowing.
Likewise, the physiological effects lipid nanoparticles (LNPs) are still mysterious. First, the exact composition isn't known or even revealed in the FDA filing (thus the "most likely" above). Second, even given known composition, there's no way to know how large, how stable, or how aggregated these particles are or what any of that means.
The model for LNPs that gets most widely discussed is an artificial cell membrane. There's a water-filled center surrounded by a bilayer of lipid (grease). These particles may show variable sensitivity to degradation depending on how administered, composition, size, shape, trace impurities, and so on. For example, Moderna's vaccine contains cholesterol, presumably for the same reason our cells do - to modulate membrane fluidity. It's not clear just yet how persistent LNPs might be and what effects they might show, separate from the RNA payload.
You say 'there's no way to know how large, how stable, or how aggregated these particles are or what any of that means', but they have been working with them for years.
Of course they could be lying or hiding information, but it seems like researching them is a way to know things about them.
True - in vitro and in limited human studies. But not at scale in human subjects. That's just this year. Studying this kind of thing is new as far as therapeutics go.
Your statement is wrong, and I’m glad you welcomed being corrected. Have a nice day.
https://www.cbsnews.com/news/covid-vaccine-pfizer-phase-3-hu...
Two U.S. pharmaceutical giants, Pfizer and Moderna, are in the final phase of coronavirus vaccine development, and Oxford University is expected to start large-scale human trials of its vaccine in the U.S. this month.
https://fda.report/media/144673/Moderna+COVID-19+Vaccine+rev...
This applies not just to any drug you take, but also to the ingredients in the food you eat and the particles in the air we breath. We've come to such realizations before, and we will again.
But we also know for sure that COVID-19 is killing people right now.
There is a small possibility that there could be detrimental effects to a fetus, which is why the vaccines are not currently recommended for pregnant women. It's not expected that there would be a negative effect; it just hasn't yet been tested. (Fortunately pregnancy is not a chronic condition, so people can still be vaccinated after giving birth.)
Do you have sources for those claims?
Now again it is possible that side effects could still be discovered in patients with complicating factors that weren't represented in the trials (like pregnancy or other known or unknown pre-existing conditions). Or just because the effects were too rare to show up significantly in the trials. But again these would be expected to show up quickly as widespread vaccination begins, as did the few severe allergic reactions that have occurred.
Of course as with anything, especially as charged an issue as vaccines, if one goes looking for it one can find plenty of purported evidence that long-term side-effects (by which I mean here side effects that don't show up until long after the vaccine is taken) are possible or even common. But the expert consensus based on the totality of evidence appears to be that this is not a serious concern.
https://www.youtube.com/watch?v=4bOHYZhL0WQ
Just to be clear, since this sounds conspiratorial - it is most likely difficult to search because 60 minutes is a copyrighted show and they have an official YT channel but only carries segments of their episodes. So, I suspect it is quite difficult to find any full episode.
https://www.cdc.gov/vaccinesafety/concerns/guillain-barre-sy...
> I recall a famous drug that was given in the 70s and it produced birth malformations.
You’re probably referring to thalidomide.
> What if someone has for XYZ reason more reverse transcriptase than usual? Will his-her DNA be altered?
Highly unlikely since the vaccines don’t code for transposable elements that could integrate into the host genome.
From what I saw, currently there's no recommendation either way for pregnant people; but everyone is watching this group carefully.
My wife and I are trying to conceive and it's such a tough call whether or not she should get vaccinated. I try to read everything, even though I know the answer is "nobody knows." While we wait for more evidence we'll continue to quarantine and stay safe. We're hoping there's a bit more evidence by the time the vaccine is available to us.
The main difference is that the way the mRNA vaccine works is much better understood. Maybe better understood,on a molecular level, than many other medications.
Normal vaccine trials is like normal software testing. Challenge testing is like running dangerous tests in production. Its faster at detecting a problem than normal tests, but ultimately not needed and can blow up badly. The argument for doing it during covid is that time was of the essence and its faster than normal testing procedures. Instead we opted for the safer slower normal testing procedure.
“Even after the vaccine is approved and licensed, regulatory agencies stay involved, continuing to monitor production; inspecting manufacturing facilities; and testing vaccines for potency, safety and purity.
The FDA also monitors adverse events that may occur related to receiving the vaccine, including through its Vaccine Adverse Event Reporting System and Phase 4 clinical trials—optional studies pharmaceutical companies may be required to perform after a vaccine is licensed to continue to monitor safety and effectiveness.” [0]
[0] https://www.jnj.com/innovation/the-5-stages-of-covid-19-vacc...
https://www.pfizer.com/news/press-release/press-release-deta...
https://www.fda.gov/media/144245/download (53 pages)
https://fda.report/media/144673/Moderna+COVID-19+Vaccine+rev... (61 pages)
I think the actual applications had a thousand pages or so, but I haven't found them online.
https://clinicaltrials.gov/ct2/show/NCT04368728 (Pfizer, >40000 participants)
https://clinicaltrials.gov/ct2/show/NCT04470427 (Moderna, 30000 participants)
I am not claiming any expertise here - I majored in Biochemistry but never finished (moved to tech). I do have 14 doctors / geneticist / infection disease specialist in my family that share this view.
This seems like a logical leap to me. Yes we need to do something to make us less open to viral threats, but you don’t present any evidence that improved computer simulations can be a useful tool in helping develop/test vaccines faster.
https://en.wikipedia.org/wiki/Computational_biology
https://a16z.com/2020/06/14/folding-at-home-supercomputer-pr...
https://www.hpcwire.com/2020/06/09/supercomputer-research-re...
https://www.ibm.com/blogs/ibm-anz/supercomputing-a-covid-19-...
https://www.cnn.com/2020/03/19/us/fastest-supercomputer-coro...
A simple search will yield months of reading. Just go to an HPC conference like SCinet (https://en.wikipedia.org/wiki/SCinet) and you will see besides energy, nukes and AI biological research is a key use of the computing power.
It also does not really seem to be supported by the evidence that things will never get back to normal if we don't do something radically different. We have a vaccine, there is no indication that we can't just distribute it and put this pandemic to bed.
I was talking with a doctor friend that oversees an ambulatory care group for the county, and they were able to allocate vaccines for the EMTs (first-responders).
Over 50% refused to be vaccinated.
Not sure how we overcome that.
I am especially baffled by the anti-vaccination movement, as I grew up in a world where smallpox and polio had been basically erradicated due to vaccinations as were most of the typical childhood diseases. But where all the victims of those diseases were not forgotten yet. There was no doubt whatever to be vaccinated, I still can remember the polio vaccinations I got in school. And those were ridiculously risky compared to a modern Covid-19 vaccination. But overall the vaccinations saved so many more people than they harmed.
One can only hope that the next months will bring a change. On the one side, there will still be many deaths due to Covid-19, as the death spike follows 4-8 weeks after the infection count spike. On the other side, in two months the effect of the vaccinations should become very visible.
The other concern I have are these cases with mild symptoms, but then becomes a psychotic issue several months later.
It seem to affect a small percentage, but a small percent of a big number can still be a big number.
https://www.nytimes.com/2020/12/28/health/covid-psychosis-me...
Do these folks also refuse to wear masks and gloves when doing their job?
I think there's a substantial difference between wearing PPE and vaccination, both on the employer's side as well as the individual employee's perspectives. Mandating proper use of PPE can never have unintended side effects. No adult has ever died from improper use of an n95 face mask or nitrile gloves. The jury on the new vaccines is going to be out for a while on long term effects. It's not reasonable for an employer to require them yet.
Besides, that would spread the legal burden to the employer were something to go wrong.
- reporting of the initial outbreak in Wuhan was too slow, but still, many countries acted in time.
- whenever a local outbreak of a similar new disease is reported, all countries should immideately go on an alert level, so that when the disease starts to spread, they can act immediately. If efficient reactions had been taken in January, a lot of things had been easier.
- of course watch international travel closely. If you close down flights, close down all travels. It doesn't make sense to ban flights from China, when the virus was coming to the US from Italy. It doesn't make sense to ban EU travellers but allow them to enter relaying via Turkey. Even better: don't ban flight travel, but test on arrival, make a short quarantine mandatory, that is more effective.
- lock down quickly and hard where neccessary, especial with local outbreaks
and the by far biggest elephant in the room:
- better hygene overall. Everyone should own proper masks, FFP2 masks should be stock piled by the government in generous amounts. Going forward, if you have symptoms of any infectious disease, wear a fucking mask! Even if it is the common cold, there is absolutely no justification to spread them to strangers. Even if it is not a deadly pandemic, infectious diseases could be reduced considerably by masks and hand sanitizing/washing. The yearly flu is deadly enough, there are no reasons to let it spread so freely.
I also hope, it becomes the new default to stay at home and work from there, if you have any symptoms. I don't know how many colds is picked up in the office in previous years.
All the involved should be harshly critisized for that.
However this should not be taken as an excuse to deny all good scientific information we have received and the right measures that have been recommended, especially the overly late committment to masks.
At the end of the day, these are all still political animals.
We still don’t have readily available N95 masks for ‘normal’ prices from reputable vendors.
Why they didn't encourage people to just use makeshift masks, is another discussion entirely.
They correctly estimated that compliance with encouragements would be very low (see e.g. current encouragements not to travel to see family at holidays).
If you tell people something that can keep them safe is available on Amazon for $25, all the encouragement in the world isn't going to keep that product from selling out.
I thought he also qualified his statement then that there was no evidence of wide scale community spread yet, but that might have been a different interview.
Regardless, it does highlight how hard it is to communicate with the public about a topic that is dynamic and fast changing.
[1] https://leadstories.com/hoax-alert/2020/05/fact-check-dr-ant...
One more thing towards rules: it really depends on a society agreeing. Like most societies agree that people should wear pants on the street, woman even shirts. There might be people breaking these rules, but overall society managed to make this a very infrequent thing.
How do you know they have less case because people follow the rules ? I have been in Cambodia and Thailand and people don't really follow the rules there and there is barely any case
What would have been easier? Germany reacted quickly and now have a lot of death
> of course watch international travel closely. If you close down flights, close down all travels
How do you close borders like the France - Switzerland that a lot of people cross everyday to go to work?
> lock down quickly and hard where neccessary, especial with local outbreaks
What do you do after the lockdown if you were not able to make it to to 0 cases?
> Going forward, if you have symptoms of any infectious disease, wear a fucking mask
there is still no proof that mask wearing did reduce the transmission of covid
you make it sounds like you have all the answers but that's not that easy
A few comments to the points you noted.
- Germany reacted at the end of February (I am from Germany), which was pretty late considering the international outbreaks, there were quite a few infections in Germany during February. But for the first wave, Germany reacted just in time to avoid a lot of deaths (<10k), but completely failed at preventing the 2nd wave. But even the first lockdown might have been prevented by acting in early february. Carnival was allowed to take place and it was one major outbreak, the other was Ischg in Austria.
- Borders to France and Swizerland had been eventually closed. When it was pretty late. But I was more referring to the US reaction, which banned travel from China only and much later (to late) from Europe, which is still in place, but allow travel via Turkey, which is what all Europeans going to the US are using.
- If you handle local outbreaks quickly, you can get infections down to 0 in the affected region.
- There is plenty of evidence, that masks reduce the transmission of Covid-19, but I was also speaking in a general sense, as I said "any infectious disease". There is no need to spread the cold or flu as quickly as we used to do. As far as I know, since the pandemic, the flu numbers are down a lot, as hygene works.
This is not true for a country like Germany, you would have to hard lockdown for some time and close all borders, and then verify any person who cross the border, and free move in Europe won't make that possible unless all EU countries do it. If you are an island things gets easier in that matter.
The ONLY country which were able to go to zero after a big outbreak is China
Also, in the clinical trials they test the actual produced vaccine, with all errors included.
[1] https://international.neb.com/tools-and-resources/selection-...
RNA has a tendency to accumulate mutations quickly, as evidenced by the many hundreds of variants of SARS-CoV-2 that have already been sequenced (and that's with only ~30,000 bases).
See: https://www.ncbi.nlm.nih.gov/books/n/nap599/ddd00075/#ddd000... and the entire article for the problem.
which is why, in the US, there is a "no-fault" fund:
https://www.hrsa.gov/vaccine-compensation/index.html
All vaccines have a risk of allergic reactions. This is why you're supposed to be monitored for at least 10 minutes after the injection. This is especially important for people who have a history of such reactions to vaccines.
[1] Section 6.3.3.2.2.1. in https://www.fda.gov/media/144246/download
[2] Table 23, Ibid.
That's why an Emergency Use Authorization is just that - there's an emergency. The FDA is well aware that long term safety is still unclear, but given the circumstances, the risks posed by vaccination for the general public are outweighed by the benefits.
" but given the circumstances, the risks posed by vaccination for the general public are outweighed by the benefits. "
That's the problem, we don't. We don't know what the risk is long term, it is unknown. It is illogical to say that an completely unknown risk has any logical comparison.
This is more uncertainty than the FDA would accept in the usual course of events - but this is an unusual time. The FDA has no adequate, approved, and available alternatives to the emergency authorization when faced with the pandemic. The investigational vaccine appears to be safe and effective against COVID-19 for the general population. Yes, the vaccine poses some unknown risks, but they are very likely vanishingly smaller than the very present health risks posed by the pandemic. For any given individual, they're much more likely to suffer negative health outcomes within the next 5 years from COVID than from the vaccine. Nobody is stating that risk to be zero. But that also doesn't mean "the risk is completely unknown so why even bother?"
How is the emergency authorization any different from an approval? If tomorrow an effective treatment for COVID-19 were to be approved or the pandemic ends, the EUA for the vaccine would be rescinded. Pfizer/Moderna must also track any adverse reactions more closely, and report them to the FDA on an ongoing basis. They also cannot sell them to private players - they're being provided to the FDA & their authorized parties. The vaccines are not licensed for COVID or any other use.